DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 22 December 2025, directing entry of the amendments original filed (after final) on 20 November 2025, has been entered. Claims 24 and 32-35 have been amended, and claim 36 has been canceled. All prior rejections of claim 36 are moot in view of the cancelation of that claim. Claims 24-35 and 37-43 are now under consideration herein. Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the following objections/rejections set forth in the prior Office action:
The rejection of claim 32 under 35 USC 112(b), in view of applicant’s clarifying amendment;
The rejections of claims under 35 USC 103, because the prior art does not teach or suggest a method comprising a “genotyping” and “detecting” meeting all requirements of amended independent claim 24; and
Several nonstatutory double patenting/provisional nonstatutory double patenting rejections (specifically those applied with regard to US patent 9,388,472 and co-pending applications 18/081,586 and 16/799,797), in view of the amendment of claim 24 to require that “the detecting excludes LOH loci from a human X/Y sex chromosome pair and human chromosome 17” (with Applicant’s arguments regarding this amendment [see Reply at page 9] being found persuasive).
Claims 24-35 and 37-43 remain rejected for the reasons given below. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is non-final.
Claim Rejections - 35 USC § 112(b)/second paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 24-35 and 37-43 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 24-35 and 37-43 are indefinite over the recitation in independent claim 24 (see (b)) of the limitation “detecting at least one LOH region in the genomic DNA based on the at least 10,000 LOH loci genotyped in (a) that have a homozygous genotype, wherein the detecting excludes LOH loci from a human X/Y sex chromosome pair and human chromosome 17”. The limitation “the at least 10,000 LOH loci genotyped in (a) that have a homozygous genotype” lacks antecedent basis, as the claim previously states “genotyping at least 10,000 LOH loci as having a heterozygous or homozygous genotype”; it is thus not clear what “at least 10,000 LOH loci…that have a homozygous genotype” are being referenced, and it is also not clear whether the “genotyping” of the claim even requires/results in something meeting this limitation of (b) of the claim (such that it appears that an element/step of some type may be missing from the claim). Further, given this lack of clarity, it is not clear what is actually encompassed by the “detecting” of (b) with regard to the type of LOH loci that must be detected (although it is noted that the length of the “LOH region” is made sufficiently clear by the claim language); further clarification is therefore needed to ensure that the boundaries of the claims are clear with regard to the required properties of the LOH loci detected via the “detecting” of (b).
Claims 33-35 are indefinite over the recitation in each of the claims of the limitation “the at least one LOH regions”, because claim 24 recites “at least one LOH region”, but does not reference “at least one LOH regions” (such that proper antecedent basis is lacking). The claims should be amended to clarify how the “detecting” of claim 24 is further limited with regard to the nature of the “at least one LOH region” that must be detected.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 24-35 and 37-43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Independent claim 24 recites a method “for detecting at least one loss of heterozygosity (LOH) region in genomic DNA” comprising - following a step (a) of “genotyping at least 10,000 loci as having a heterozygous or homozygous genotype from at least one pair of human chromosomes in the genomic DNA” using DNA sequencing - “detecting at least one LOH region in the genomic DNA based on the at least 10,000 LOH loci genotyped in (a) that have a homozygous genotype, wherein the detecting excludes LOH loci from a human X/Y sex chromosome pair and human chromosome 17, wherein the at least one LOH region is longer than 5 megabases but shorter than the length of the whole chromosome containing the at least one LOH region”. Such a “detecting” - which is unclear/indefinite with regard to what it specifically requires, as noted above - may be conducted entirely in the human mind, for example by thinking about the results of the previously recited “genotyping…using sequencing”, such that the claims are directed to an abstract idea. More particularly, the result of the “genotyping” of (a) encompasses, e.g., sequencing data in any format regarding “at least one pair of human chromosomes”, and the “detecting” as presently claimed requires nothing manipulative/active in nature, but rather encompasses activities such as inspecting and drawing conclusions from gathered data; further, such a “detecting” is also sufficient to accomplish the “detecting” of the preamble of the claim.
This judicial exception is not integrated into a practical application because the “genotyping….using sequencing” activities of the claims are insignificant extrasolution activity that achieve the gathering of data/information, rather than any kind of implementation /application of the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only active step of the claim - which recites genotyping LOH loci by “using DNA sequencing” – embraces activities recognized by the courts as constituting well-known, routine and conventional activities in the life science arts when claimed at a high level of generality (as is the case here); see MPEP 2106.05(d)(II), and particularly Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014). It is noted that the prior art as exemplified by Nielsen et al (Nature Reviews: Genetics 12:443 [June 2011; online May 2011]; previously cited) and Cirulli et al (Genome Biology 11:R57 [May 2010]; previously cited) further establish that the use of whole-genome/next generation sequencing to perform genomic sequencing/genotyping/SNP calling were well-understood, routine, and conventional activities as of Applicant’s effective filing date. Furthermore, while it is noted that the prior art does not teach methods including genotyping and “detecting” as presently recited in the claims, the required “detecting” is abstract in nature as noted above, and thus neither implements/applies a JE, nor adds something “significantly more”. An inventive concept cannot be furnished by a judicial exception (i.e., a law of nature/natural phenomenon/abstract idea) itself (see MPEP 2106.05(I)).
With regard to dependent claims 25-29, these claims simply recite further general categories/types data gathering achieved by DNA sequencing; nothing amounting a practical application or something “significantly more” than a JE is added (see, e.g., Nielsen et al and Cirulli et al [previously cited] regarding the fact that such sequencing types correspond to well-understood, routine, and conventional activity). Claim 30 and claims dependent therefrom (claims 31 and 37-43) are only necessarily further limiting of the source of genomic DNA for testing/genotyping, which is an element of the data gathering activities of the claim (rather than something that implements a JE, or adds something “significantly more”). Claims 32-35 recite characteristics of an LOH region or regions in tested genomic DNA; nothing related to application/implementation of a JE is required, nor do these claims set forth anything further amounting to something “significantly more” than a JE. Thus, none of claims 24-35 and 37-43 is directed to patent eligible subject matter.
The reply of 22 December 2025 (incorporating arguments filed 20 November 2025) traverses the prior rejection of claims under 35 USC 101 on the following grounds. Applicant urges that the claims as amended – with independent claim 24 now reciting “genotyping at least 10,000 LOH loci” – is “a process that cannot practically be performed in the human mind” (Reply page 8). Applicant thus further argues that “claim 24 and its dependencies do not recite an abstract idea, nor are they directed to one” (Reply page 8).
These arguments have been thoroughly considered but are not persuasive. While the examiner concurs that the “genotyping” as claimed cannot be performed in the human mind, this element of the claim (as discussed above) corresponds to routine data gathering, i.e., insignificant extrasolution activity, and also does not add something “significantly more” than a JE (again, as discussed in the above rejection of the amended claims). Accordingly, this argument is not found persuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 24-35 and 37-43 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of copending Application No. 19/088,442 (now published as US 20250250643A1 [previously cited]). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. Instant independent claim 24 as amended is drawn to a method for detecting at least one LOH region, comprising “(a) genotyping at least 10,000 LOH loci as having a heterozygous or homozygous genotype from at least one pair of human chromosomes….using DNA sequencing”, and “detecting at least one LOH region in the genomic DNA based on the at least 10,000 LOH loci genotyped in (a) that have a homozygous genotype, wherein the detecting excludes LOH loci from a human X/Y sex chromosome pair and human chromosome 17, and wherein the LOH region is longer than 5 megabases but shorter than the length of the whole chromosome containing the at least one LOH region” (see b) of the claim). The ‘442 claims, and particularly claim 13 and claims dependent therefrom, are directed to methods comprising “sequencing genomic DNA from a cancer cell” to produce sequencing results, genotyping “at least 1,000 loci in the DNA sequencing results as having a heterozygous or homozygous genotype, wherein the loci are not in a human X/Y sex chromosome pair”, and “detecting at least one indicator LOH region in the genomic DNA based on homozygosity of loci genotyped…wherein the indicator LOH region is longer than 1.5 megabases but shorter than the length of the whole chromosome containing the indicator LOH region”. The two sets of claims thus embrace the same general activities of genotyping via sequencing/sequencing to achieve genotyping and “detecting” features based on the generated genotyping/sequencing data. While the ‘442 claims differ from instant independent claim 24 in some respects, it is noted that the ‘442 dependent claims recite the preferred minimum LOH region length of instant claim 24 (see, e.g., ‘442 claim 14), as well as the exclusion of chromosome 17 now recited in instant claim 24 (see, e.g., ‘442 claim 25). The ‘442 claims also recite cancer cell types corresponding to the preferred cell types of the instant claims (see, e.g., instant dependent claims 30-31 and 37-43), and otherwise set forth preferred embodiments that mirror those of the instant claims with regard to LOH region length, chromosome pair numbers, etc. While instant claim 24 has been amended to require genotyping ‘at least 10,000 LOH loci”, which differs from the maximum number of loci specified in the ‘442 claims (of “at least 1,000 loci”; see ‘442 claim 13), an ordinary artisan would have recognized that “at least 1,000 loci” embraces embodiments including any number of loci larger than 1,000, including “at least 10,000 loci” as set forth in the instant claims, and further that the type of sequencing recited in the ‘442 claims would embrace generation of sequencing data including information regarding such larger numbers of loci. Thus, this difference does not render the instant claims patentably distinct from the ‘442 claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The reply of 22 December 2025 (incorporating the arguments filed 20 November 2025) traverses the rejection on the grounds that the amended instant claims include limitations not required by the co-pending claims (Reply page 9). With regard to the exclusion of a human X/Y chromosome pair and human chromosome 17, this is not accurate with regard to the ‘442 claims (as noted in the above revised rejection). Further, the difference in number of LOH loci genotyped is not persuasive with regard to the instant claims being patentably distinct from the ‘442 claims, given that the ‘442 claims encompass “at least 1,000 loci” (which encompasses, and also reasonably suggests, larger number of loci). Thus, while Applicant’s arguments were found persuasive with regard to several other nonstatutory double patenting rejections, the instant rejection is maintained.
Conclusion
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682